Die Behandlung der akuten lymphoblastischen Leukämie im Kindes- und Jugendalter: Ergebnisse der multizentrischen Therapiestudie ALL-BFM 81*

Abstract

In therapy study ALL-BFM 81 633 previously untreated patients with acute lymphoblastic leukemia (ALL) less than 18 years of age have been recruited from April 1, 1981 to September 30, 1983 and treated in 37 institutions throughout West-Germany and Austria. Here only therapy results of 611 patients with non-B-ALL are presented. Patients with ALL of B-type are described elsewhere. In this fourth consecutive trial of the BFM study group three major questions have been asked: 1. Is it possible to assess the individual risk for relapse more accurately by the use of a risk factor rather than by the risk score which was the discriminator in studies ALL-BFM 76 and ALL-BFM 79? Does this risk factor discriminate more precisely patients at the highest risk for relapse? Offers more intensive risk-adapted therapy to this patient group a better chance for disease-free survival? 2. In patients at a standard risk for relapse with a risk factor below 1.2--approximately 60% of patients with non-B-ALL--can radiotherapy for prevention of CNS disease effectively be replaced by chemotherapy (intermediate dose Methotrexate)? 3. It is possible to reduce duration of maintenance therapy by 6 months to a total duration of 18 months with no unfavorable effect? To assess the radiation problem in standard risk patients and to evaluate the importance of duration of maintenance therapy two randomisations have been utilized. After a median duration of study ALL-BFM 81 of 4 1/2 years and 3 1/4 years after the study had been closed (date of evaluation January 1, 87) the answers are as follows: 1. For the majority of patients risk-adapted therapy had a curative effect. The probability for event-free survival (EFS) in standard risk patients in slightly above 70%, in medium risk patients 67%. In high-risk patients risk-adapted therapy did not improve prognosis, the EFS being still in the order of 50%. A good assessment of the individual risk for relapse is possible by the newly introduced risk factor. This principle is superior to the risk score used in former studies ALL-BFM 76 and ALL-BFM 79 because a low risk group (risk factor below 0.8) could be identified including approximately 25% of all patients with non-B ALL. Selection, quality, and timing of therapy elements remain the decisive prognostic factors, however. 2. Standard risk patients with a risk factor below 0.8 can effectively be protected for CNS relapse by treatment with intermediate dose Methotrexate.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

“…Details regarding dosage and exact timing are provided in the key references published earlier [13][14][15]17,21 and are provided in Supplementary Tables 1-5. The major study questions addressed in each trial are summarized under section Introduction.…”

“…In induction, prednisone has been applied at a daily dose of 2.5 mg/kg or 60 mg/m 2 for 28 days (followed by a tapering-down phase) since trial ALL-BFM 70. 2,4,5,13 Beginning with trial ALL-BFM 83, induction therapy was started with a 1-week prednisone window to evaluate the in vivo response to treatment, and to avoid morbidity from tumor lysis syndrome a stepwise increase to full dose was allowed. 14 DEXA has been used for re-intensification for 2 weeks (plus tapering down) in Protocol III at 10 mg/m 2 /day (in trial ALL-BFM 70-79 with 15 mg/m 2 /day), for 4 weeks (plus tapering down) in Protocol II of studies ALL-BFM 81 and 83, and for 3 weeks in Protocol II in studies ALL-BFM 86, 90 and 95.…”

“…and (2) Can the total treatment duration be shortened by 6 months of maintenance therapy from 24 to 18 months? 13 In addition, overall improvement was sought by increasing anthracycline dose from 25 to 30 mg/m 2 and in HR patients by introducing an extended re-intensification element. 8 In study ALL-BFM 83, patients were stratified as in the previous trial and the study focused again on reduction of treatment burden in SR patients with the following randomized questions: (1) Can the 4-week re-intensification element Protocol III be omitted in the 28% of patients defined as SRlow (SR-L) (BFM-RFo0.8)?…”

Primary hepatic tumours in children: A 26—year review

“…One patient with NHL was treated according to the Berlin, Frankfurt, Munster Acute Lymphoblastic Leukaemia (BFM-ALL) 81 protocol [3] following initial biopsy. Five patients (HBL, 4; RMS, 1) also received elective chemotherapy (Table IV) following surgery.…”

Neurophysiological findings in long-term survivors of acute lymphoblastic leukaemia in childhood treated with the BFM protocol 81 SR-A/B

“…risk factor <1.2) without leukaemic CNS involvement were included. All of them were in ®rst complete continuous remission and had been treated according to the therapy protocol BFM-81 [13]. Antileukaemic treatment consisted of an induction and consolidation phase of 4 weeks duration each, CNS prophylaxis, an intensi®ed re-induction period and maintenance treatment of 18 or 24 months duration (Table 1).…”